Amyotrophic lateral sclerosis disease modifying therapeutics:a cell biological perspective

Amyotrophic lateral sclerosis（ALS）is a progressively fatal neuromuscular disorder classically characterized by loss of upper and lower motor neurons from the cortex to the spinal cord Diagnosed patients have a median survival of about 3 years and death usually results from eventual respiratory failure.

Modified upper abdominal cluster transplantation in patients with end-stage liver diseases associated with insulin dependent type 2 diabetes mellitus

Objective Modified upper abdominal cluster transplantation ( MCT) ,which was inspired by classical cluster transplant technique,has been proven more effective and feasible in the treatment of patients with end stage liver diseases associated with insulin - dependent

Promises and pitfalls of immune-based strategies for Huntington's disease

Huntington＇s disease （HD） is an autosomal-dominant neurodegenerative disease characterized by the selec- tive loss of neurons in the striatum and cortex, leading to progressive motor dysfunction, cognitive decline and behavioral symptoms. HD is caused by a trinucleotide （CAG） repeat expansion in the gene encoding for huntingtin. Several studies have suggested that inflammation is an important feature of HD and it is already observed in the early stages of the disease. Recently, new molecules presenting anti-inflammatory and/or immunomodulatory have been investigated for HD. The objective of this review is to discuss the data obtained so far on the immune-based therapeutic strategies for HD.

Promoting remyelination for the treatment of multiple sclerosis:opportunities and challenges

Multiple sclerosis （MS） is a chronic and devastating autoimmune demyelinating disease of the central nervous system. With the increased understanding of the pathophysiology of this disease in the past two decades, many disease-modifying therapies that primarily target adaptive immunity have been shown to prevent exacerbations and new lesions in patients with relapsing-remitting MS. However, these therapies only have limited efficacy on the progression of disability. Increasing evidence has pointed to innate immunity, axonal damage and neuronal loss as important contributors to disease progression. Remyelination of denuded axons is considered an effective way to protect neurons from damage and to restore neuronal function. The identification of several key molecules and pathways controlling the differentiation of oligodendrocyte progenitor cells and myelination has yielded clues for the development of drug candidates that directly target remyelination and neuroprotection. The long-term efficacy of this strategy remains to be evaluated in clinical trials. Here, we provide an overview of current and emerging therapeutic concepts, with a focus on the opportunities and challenges for the remyelination approach to the treatment of MS.

Coexisting ankylosing spondylitis and rheumatoid arthritis： A case report with literature review

A 30-year-old female patient with coexisting ankylosing spondylitis and rheumatoid arthritis was diagnosed and treated. The human leukocyte antigen （HLA）-B27 is a predisposing factor of ankylosing spondylitis and HLA-DR4 is a predisposing factor of rheumatoid arthritis. This patient was HLA-B27 and HLA-DR4 positive, and ankylosing spondylitis manifested before rheumatoid arthritis. After disease modifying anti-rheumatic drugs successfully arrested ankylosing spondylitis activity the patient conceived and delivered a healthy baby. One year later, she developed peripheral polyarthritis and was diagnosed with rheumatoid arthritis. We hypothesized that pregnancy may be one of the environmental factors that can activate rheumatoid arthritis, and that disease modifying anti-rheumatic drugs play an important role in keeping the disease under control.

Disease modification and Neuroprotection in neurodegenerative disorders

Background:Disease modifying therapies(DMTs)are urgently needed for neurodegenerative diseases(NDD)such as Alzheimer’s disease(AD)and many other disorders characterized by protein aggregation and neurodegeneration.Despite advances in understanding the neurobiology of NDD,there are no approved DMTs.Discussion:Defining disease-modification is critical to drug-development programs.A DMT is an intervention that produces an enduring change in the trajectory of clinical decline of an NDD by impacting the disease processes leading to nerve cell death.A DMT is neuroprotective,and neuroprotection will result in disease modification.Disease modification can be demonstrated in clinical trials by a drug-placebo difference in clinical outcomes supported by a drug-placebo difference on biomarkers reflective of the fundamental pathophysiology of the NDD.Alternatively,disease modification can be supported by findings on a staggered start or delayed withdrawal clinical trial design.Collecting multiple biomarkers is necessary to support a comprehensive view of disease modification.Conclusion:Disease modification is established by demonstrating an enduring change in the clinical trajectory of an NDD based on intervention in the fundamental pathophysiology of the disease leading to nerve cell death.Supporting data are collected in clinical trials.Effectively defining a DMT will assist in NDD drug development programs.

Vedolizumab for chronic antibiotic-refractory pouchitis

Background:Chronic antibiotic-refractory pouchitis(CARP)is a complication of ileal pouch-anal anastomosis(IPAA),which poses a therapeutic challenge.Vedolizumab,a gut-selective monoclonal antibody to the a4b7 of integrin,has been used in such patients,but data on its efficacy are limited.Our aim was to assess the efficacy and safety of vedolizumab as induction therapy in CARP patients.Methods:In this single-center,historic cohort,patients with CARP who received vedolizumab between January 2015 to June 2017 were identified and analysed.Patients were included if they had active pouchitis with a total of modified pouch disease activity index(mPDAI)score5 or if unavailable clinician diagnosis of active pouchitis.Pre-treatment and at 3-month posttherapy pouchoscopy and clinical visits were used to calculate mPDAI.Results:A total of 19 patients were included in the study.The mean age was 26.7612.8 years,with 10(53%)males.Nine(47%)patients had been treated with anti-tumor necrosis factor(TNF)agents before colectomy and 10(53%)had anti-TNFs after colectomy and IPAA.Six(32%)patients had improvement in the mPDAI symptom subscores(P=0.031)and 14(74%)had improvement in both endoscopic and total mPDAI scores with a median change of-2 units(both P=0.031).Adverse events were noted only in two(11%)patients and four(21%)required surgery for CARP.Conclusions:Our study suggests that vedolizumab has efficacy and can be safely used for CARP patients.Larger studies with a higher number of patients are required to confirm these findings.